TY - JOUR
T1 - A mutation in the Golgi Qb-SNARE gene GOSR2 causes progressive myoclonus epilepsy with early ataxia
AU - Corbett, Mark A.
AU - Schwake, Michael
AU - Bahlo, Melanie
AU - Dibbens, Leanne M.
AU - Lin, Meng
AU - Gandolfo, Luke C.
AU - Vears, Danya F.
AU - O'Sullivan, John D.
AU - Robertson, Thomas
AU - Bayly, Marta A.
AU - Gardner, Alison E.
AU - Vlaar, Annemarie M.
AU - Korenke, G. Christoph
AU - Bloem, Bastiaan R.
AU - De Coo, Irenaeus F.
AU - Verhagen, Judith M.A.
AU - Lehesjoki, Anna Elina
AU - Gecz, Jozef
AU - Berkovic, Samuel F.
N1 - Funding Information:
We are grateful for the cooperation of the families involved in this study. Thank you to Maike Langer, Thomas Hoefken, Lisa van Winsen, Maria Digenis, Bev Johns, and Rob King for excellent technical assistance; Paul Saftig for valuable advice; and Johannes Aerts for kindly providing us with the anti-human β-GC antibody 8E4. M.B. and J.G. were supported by the National Health and Medical Research Council (NH&MRC) with a Career Development Award and a Principal Research Fellowship, respectively. This project was supported by NH&MRC program grant 400121 and by the Research Training Group (GRK1459), funded by the Deutsche Forschungsgemeinschaft (DFG) to P.S. and M.S. The study was approved by the Austin Health Human Research Ethics Committee and informed consent was obtained from all participants.
PY - 2011/5/13
Y1 - 2011/5/13
N2 - The progressive myoclonus epilepsies (PMEs) are a group of predominantly recessive disorders that present with action myoclonus, tonic-clonic seizures, and progressive neurological decline. Many PMEs have similar clinical presentations yet are genetically heterogeneous, making accurate diagnosis difficult. A locus for PME was mapped in a consanguineous family with a single affected individual to chromosome 17q21. An identical-by-descent, homozygous mutation in GOSR2 (c.430G>T, p.Gly144Trp), a Golgi vesicle transport gene, was identified in this patient and in four apparently unrelated individuals. A comparison of the phenotypes in these patients defined a clinically distinct PME syndrome characterized by early-onset ataxia, action myoclonus by age 6, scoliosis, and mildly elevated serum creatine kinase. This p.Gly144Trp mutation is equivalent to a loss of function and results in failure of GOSR2 protein to localize to the cis-Golgi.
AB - The progressive myoclonus epilepsies (PMEs) are a group of predominantly recessive disorders that present with action myoclonus, tonic-clonic seizures, and progressive neurological decline. Many PMEs have similar clinical presentations yet are genetically heterogeneous, making accurate diagnosis difficult. A locus for PME was mapped in a consanguineous family with a single affected individual to chromosome 17q21. An identical-by-descent, homozygous mutation in GOSR2 (c.430G>T, p.Gly144Trp), a Golgi vesicle transport gene, was identified in this patient and in four apparently unrelated individuals. A comparison of the phenotypes in these patients defined a clinically distinct PME syndrome characterized by early-onset ataxia, action myoclonus by age 6, scoliosis, and mildly elevated serum creatine kinase. This p.Gly144Trp mutation is equivalent to a loss of function and results in failure of GOSR2 protein to localize to the cis-Golgi.
UR - http://www.scopus.com/inward/record.url?scp=79955868512&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2011.04.011
DO - 10.1016/j.ajhg.2011.04.011
M3 - Article
C2 - 21549339
AN - SCOPUS:79955868512
SN - 0002-9297
VL - 88
SP - 657
EP - 663
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 5
ER -